查找使用阿拉丁产品的科研文献

Icariin delivery system based on covalent organic framework materials: dual effects of immune modulation and osteogenesis promotion

Mingdong Luo,Xueqing Lin,Na Wang,Qishan Xie,Shiyi Zeng,Shiting Li,Zhoukun He,Xiaorong Lan

Bone defects, induced by trauma, infection, tumor resection, osteoporosis, and congenital deformities, severely affect patient health both physiologically and psychologically, imposing substantial burdens on healthcare systems and public resources. Bone defect repair involves a complex biological process that orchestrates events such as immune modulation and osteogenic differentiation. Consequently, ideal materials for bone defect regeneration should possess capabilities in both immune regulation and osteogenesis. In this study, we synthesized a kind of covalent organic framework (COF) nanoparticles at room temperature and modified their surface with polydopamine (PDA), resulting in PDA-functionalized COFs (PCOFs). Utilizing the adhesive properties of PDA, we successfully loaded icariin (ICA) onto the PCOFs nanoparticles, forming ICA@PCOFs. Comprehensive characterization techniques, including visual inspection, scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA), confirmed the successful synthesis of ICA@PCOFs nanoparticles. Subsequent optimal concentration determination via the CCK-8 assay, and further experiments including alkaline phosphatase (ALP) activity, alizarin red S (ARS) staining, and immunofluorescent staining for osteocalcin (OCN), runt-related transcription factor 2 (Runx2), inducible nitric oxide synthase (iNOS), and mannose receptor (CD206), assessed their capability to modulate macrophage polarization and promote osteogenesis. The results revealed that ICA-loaded nanoparticles demonstrated significant potential in vitro for immune regulation and promoting stem cell osteogenic differentiation. These findings suggest that ICA@PCOFs nanoparticles could represent a promising therapeutic platform for bone defect regeneration, offering dual functionalities in immune modulation and osteogenesis promotion.

Exploring the molecular mechanism of icariin improving spinal cord injury through network pharmacology combined with experimental verification

Zhou Mengmeng,Jiang Zehua,Zhang Maosen,Feng Sa,Ma Boyuan,Kan Shunli,Fu Xuanhao,Zhu Rusen

This study aimed to investigate the potential pharmacological effects of icariin (ICA) in the treatment of spinal cord injury (SCI). Network pharmacology was used to focus on the potential targets and biological processes of ICA in SCI. Molecular docking was used to verify the ability of ICA to bind to its core targets. Finally, valuate the efficacy and potential mechanisms of ICA in treating spinal cord injury through in vitro and in vivo experiments. A total of 37 targets were screened out, and core genes were screened out from the protein‒protein interaction network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that these targets are enriched mainly in response to hypoxia, regulation of the cellular response to stress, and the TGF-beta signaling pathway. Molecular docking analysis showed that ICA has good docking ability with core targets. In animal experiments, Basso, Beattie and Bresnahan scores, catwalk gait analysis, hematoxylin and eosin staining, and RT-qPCR showed that ICA can inhibit spinal cord inflammation and effectively improve the behavioral and histological recovery after SCI rats. Western blot and immunofluorescence showed that ICA can reduce astrocyte activation and downregulate the TGF-beta signaling pathway after SCI. In addition, ICA can promote axonal nerve elongation and promotes angiogenesis after spinal cord injury in rats. In vitro experiments revealed that ICA can inhibit TGFβ1-induced activation of the TGF-beta signaling pathway and astrocyte activation. ICA treats SCI through multiple targets and pathways. ICA plays a major role in protecting nerves, promoting angiogenesis, and inhibiting reactive astrocyte activation in the treatment of SCI.

Icariin ameliorates LPS-induced acute lung injury in mice via complement C5a-C5aR1 and TLR4 signaling pathways

Jing Guo,Qi-Yun Zhang,Lin Xu,Min Li,Qian-Yun Sun

Acute lung injury (ALI) is an acute respiratory-related progressive disorder, which lacks specific pharmacotherapy. Icariin (ICA) has been shown to be effective in treating ALI. However, the targets and pharmacological mechanisms underlying the effects of ICA in the treatment of ALI are relatively lacking. Based on network pharmacology and molecular docking analyses, the gene functions and potential target pathways of ICA in the treatment of ALI were determined. In addition, the underlying mechanisms of ICA were verified by immunohistochemistry, immunofluorescence, quantitative Real-time PCR, and Western blot in LPS-induced ALI mice. The biological processes targeted by ICA in the treatment of ALI included the pathological changes, inflammatory response, and cell signal transduction. Network pharmacology, molecular docking, and in vivo experimental results revealed that ICA inhibited the complement C5a-C5aR1 axis, TLR4 mediated NF-κB, MAPK, and JAK2-STAT3 signaling pathways related gene and protein expressions, and decreased inflammatory cytokine, chemokine, adhesion molecule expressions, and mitochondrial apoptosis in LPS-induced ALI.

Icariin ameliorates chronic renal failure and fibrotic injury by modulating the STING signaling pathway to promote mitophagy

Lan Xinpeng,Li Ji,Zhang Peiqing

Background Chronic renal failure (CRF) is characterized by progressive renal function decline, oxidative stress (OS), inflammation, and fibrosis, with a current lack of effective treatments. This study investigates the interventional effects of Epimedium extract (EPE) on CRF and focuses on the elucidation of its potential mechanisms of action. Methods In vivo and in vitro experiments were conducted using a CRF rat model and a TGF-β1-induced fibrosis model in human renal tubular epithelial cells (HK-2). Rats were randomly assigned to control, model, low/high-dose EPE, and EPE combined with Mdivi-1 experimental groups. HK-2 cells were grouped into control, TGF-β1, EPE-treated, and STING overexpression groups. Renal function parameters (SCR, BUN, UPR), OS markers (ROS, MDA, GSH, SOD), inflammatory cytokines (IL-1β, IL-6, TNF-α), fibrosis markers (Hyp, MMP2/9, α-SMA, Col-1, FN), autophagy-related proteins (LC3B, Beclin1, ATG5, p62), and key molecules of the cGAS-STING pathway were assessed to explore the protective effects and underlying mechanisms of EPE in CRF. Results EPE significantly improved renal function, reduced OS and inflammatory responses, alleviated pathological damage and fibrosis in renal tissues, and promoted the expression of autophagy-related proteins in CRF rats. Mdivi-1 partially reversed the protective effects of EPE, suggesting autophagy-dependent mechanisms. Mechanistically, EPE inhibited cGAS-STING pathway activation and reduced the phosphorylation of downstream TBK1 and IRF3. In HK-2 cells, EPE mitigated TGF-β1-induced apoptosis, OS, inflammation, and fibrosis, while promoting mitophagy. However, STING overexpression attenuated these protective effects. Conclusion EPE ameliorates renal dysfunction, OS, inflammation, and fibrosis in CRF by suppressing cGAS-STING signaling activation and enhancing autophagy activity. This study provides experimental evidence supporting EPE as a potential therapeutic agent for chronic kidney disease and highlights the regulatory role of the cGAS-STING pathway in renal fibrosis. Graphical abstract

Icariin-Mediated miR-875-5p Inhibits Autophagy and Epithelial-Mesenchymal Transition by Regulation of MDM4 in Cervical Cancer

Duan Ping,Cheng Jing,Mao Ruotong,Wang Ruina,Jin Yueqi,Li Chunyang

MicroRNAs, one type of non-coding RNA, and Icariin have attracted tremendous attention concerning various diseases, especially cancers. Also, the function of Icariin on malignant behaviors by targeting miR-875-5p/MDM4 axis in cervical cancer remains unknown. MiR-875-5p analogs combined with MDM4 or Icariin were used to explore autophagy and epithelial-mesenchymal transition in cancer cells. Xenograft mice were highlighted to elucidate the influences of Icariin and miR-875-5p in vivo. As a result, miR-875-5p was cut down in cervical cancer cells, which promoted malignant phenotype, autophagy, and limited apoptosis in cervical cancer cells. Contrarily,miR-875-5p overexpression had a contrary performance in cervical cancer cells. miR-875-5p was validated as a sponge of MDM4. Enhanced expression of MDM4 weakened the performance of miR-875-5p mimic on autophagy and epithelial-mesenchymal transition. Moreover, Icariin reversed the stimulative action of the inhibitor on autophagy and xenograft tumor growth. Generally, These findings imply that Icariin could be identified as a curative avenue for cervical cancer via miR-875-5p/MDM4 axis.

Intradermal injection of icariin-HP-β-cyclodextrin improved traumatic brain injury via the trigeminal epineurium-brain dura pathway

Wei Yang,Yong-Hui Han,Heng-Cai Wang,Cui-Tao Lu,Xi-Chong Yu,Ying-Zheng Zhao

Study on the effect of sustained -release icariin-loaded Graphene oxide-hydrogel composite scaffold on bone defect repair

Qingdi Qu,Qian Zhang,Mengyuan Wang,Shuang Zhao,Ping Li,Chenxi Shang,Yumei Niu,Shuang Zhang,Shuang Pan

In orthopedic treatment, long-term nonunion of bone defects has always been a significant issue. As bone graft materials, tetra-armed polyethylene glycol (Tetra-PEG) hydrogel scaffolds are anticipated to address this issue due to their extracellular matrix (ECM)-like structure. However, poor osteoinductivity and cell adhesion after implantation restricted its clinical application in bone tissue engineering. Herein, graphene oxide (GO) loaded with icariin (ICA) was loaded into the Tetra-PEG hydrogel semi-interpenetrating network composite gel by in situ composite approach, and silk fibroin (SF) was incorporated to create a new organic–inorganic composite hydrogel scaffold (PNSG-ICA) to investigate the controlled drug release characteristics and osteogenic properties. The experiments of this study demonstrate that PNSG-ICA scaffolds can effectively encapsulate and release ICA over a period of 12 days. The scaffolds exhibited interconnected porous microarchitectures, satisfactory mechanical properties, appropriate degradation characteristics, and excellent biocompatibility. In vitro analyses indicated that ICA-doped hydrogels significantly enhanced the osteogenic differentiation of rat bone mesenchymal stem cells (rBMSCs), as demonstrated by alkaline phosphatase and alizarin red staining, as well as qRT-PCR assessments. Moreover, in vivo investigations revealed that the ICA sustained-release system significantly enhanced the regeneration of bone defects mediated by rBMSCs in situ, as evidenced by mouse calvarial bone defect models. In summary, we envision that the prolonged release of ICA from PNSG-ICA scaffolds may become a new strategy for the clinical treatment of bone defects.

Smart responsive injectable hydrogel loaded with icariin inhibits ferroptosis and promotes nucleus pulposus repair in intervertebral disc degeneration

Zhidong Lin,Luoqi Mai,Huitong Luo,Zetao Wang,Yongpeng Lin,HongShen Wang,Shaohua Chen,Guoyi Su,Xulin Hu,Bolai Chen,Xiaodong Cao

Intervertebral disc degeneration (IVDD) is a leading cause of lower back pain, characterized by the ferroptosis of nucleus pulposus cells (NPCs) and imbalance in reactive oxygen species (ROS) metabolism. Icariin (ICA), an active compound from traditional Chinese medicine, scavenges ROS and inhibits ferroptosis, but its poor water solubility and low bioavailability limit clinical use. A dual-crosslinked hydrogel (HP@ICA) is developed to address these challenges. Cyclodextrin is integrated into polyvinyl alcohol to enhance ICA loading via hydrophobic interactions. Methacrylic acid and phenylboronic acid are incorporated into hyaluronic acid, enabling dynamic bonding with polyvinyl alcohol. Ultraviolet crosslinking creates a secondary crosslinked hydrogel with pH and ROS responsiveness, self-healing properties, and improved ICA solubility, increasing its water solubility tenfold. Enhanced solubility boosts ICA's free radical scavenging capacity by 103 %, suppressing ferroptosis and promoting NP cell regeneration, as demonstrated by reduced iron ion concentrations, lower malondialdehyde levels, and restored glutathione peroxidase 4 activity. Ferroptosis inhibition facilitates type II collagen production in NP cells. Mechanistic studies reveal activation of the Nrf2-GPX4 pathway as key to regeneration. These findings suggest a promising regenerative therapeutic approach for IVDD.

Icariin improves cardiac function and remodeling via the TGF-β1/Smad signaling pathway in rats following myocardial infarction

Jia Ji,Zhao Xing-an,Tao Si-ming,Wang Jun-wen,Zhang Rong-liang,Dai Hua-lei,Zhang Xin-jin,Han Ming-hua,Yang Bei,Li Yu,Li Jin-tao

Background Postinfarction cardiac remodeling presents a compensatory mechanism aimed at mitigating congestive heart failure. It is distinguished by progressive dilatation and hypertrophy of the ventricular chambers, fibrotic alterations, and prolonged apoptosis of cardiomyocytes. The primary objective of this study was to assess the effects of icariin on myocardial fibrosis and ventricular remodeling in rats subjected to myocardial infarction (MI).Methods Male Sprague‒Dawley (SD) rats were subjected to randomization and subsequently divided into distinct groups: the control group, the sham group (undergoing sham operation), the MI group (experiencing ligation of the left anterior descending artery), and the icariin group. Within the icariin group, rats were further categorized into three different dose groups based on the administered icariin dosage: the MI30 group (30 mg/kg/day), the MI60 group (60 mg/kg/day), and the MI120 group (120 mg/kg/day). Cardiac function evaluation was carried out using echocardiography. Histological examinations, including hematoxylin and eosin (HE) staining, Masson staining, and immunohistochemistry studies, were conducted 90 days after the occurrence of MI. Additionally, Western blotting was employed to assess TGF‐β1, p-Smad2, and p-Smad3 levels.Results The administration of icariin revealed a noteworthy enhancement in cardiac function among rats afflicted with left anterior descending coronary artery (LAD) ligation. In comparison to the icariin groups, the MI group exhibited reduced EF and FS, along with elevated LVEDD and LVESD. Furthermore, the cardiac fibrosis levels in the MI group rats exhibited a considerable increase compared to those in the icariin group. Notably, the levels of Collagen I, Collagen III, MMP2, and MMP9 were significantly higher in the MI group than in the icariin group, with evident distinctions. Moreover, the expression levels of TGF-β, IL-13, p-Smad2, and p-Smad3 were notably upregulated in the MI group compared to the icariin group.Conclusion sIn an experimental rat model of MI, the administration of icariin resulted in the amelioration of both cardiac function and remodeling processes, operating through the intricate TGF-β1/Smad signaling pathway.

Icariin controlled release on a silk fibroin/mesoporous bioactive glass nanoparticles scaffold for promoting stem cell osteogenic differentiation

Xiaofeng Shen,Pengfei Yu,Hua Chen,Jiangping Wang,Binjie Lu,Xuefeng Cai,Chun Gu,Guoqiang Liang,Donglin Hao,Qihan Ma,Yuwei Li

The treatment of bone defects caused by various reasons is still a major problem in orthopedic clinical work. Many studies on osteogenic implant materials have used various biologically active factors such as osteogenic inducers, but these biologically active factors have various side effects. Therefore, in this study, silk fibroin (SF) was used as a scaffold material, mesoporous bioactive glass nanoparticles (MBGNs) as a sustained release carrier, and the traditional Chinese drug icariin (ICA) was loaded to promote bone formation. The experiments in this study have proven that SF/MBGNs-ICA scaffolds can successfully load and release ICA for a long time, and the sustained-release ICA can promote the proliferation and differentiation of BMSCs for a long time. This controlled-release ICA organic/inorganic two-component scaffold material is expected to become a new bone grafting solution.

Roles of the antioxidant properties of icariin and its phosphorylated derivative in the protection against duck virus hepatitis

Xiong Wen,Chen Yun,Wang Yu,Liu Jiaguo

Background Duck viral hepatitis (DVH) is an acute disease of young ducklings with few convenient and effective veterinary drugs to treat. In pathology, present study mainly focused on the immune mechanism, but very few studies have concerned with the role of oxidative stress in the pathogenesis of DVH. To study the antioxidative and hepatoprotective effects of icariin and its phosphorylated derivative against DVH, we prepared phosphorylated icariin (p-icariin) using the sodium trimetaphosphate–sodium tripolyphosphate method. Ducklings were drunk with icariin and p-icariin after being challenged with duck hepatitis virus 1 (DHV-1). We recorded the number of dead ducklings, gross pathological changes in the liver, and changes in indices of oxidative stress and liver injury. The correlations between these indices were also analyzed.Results Exposure to DHV-1 induced significant oxidative damage in ducklings. Administration of icariin or p-icariin attenuated liver pathological injury and significantly increased the survival rate, with better outcomes in ducklings treated with p-icariin than in those treated with icariin. Icariin and p-icariin also attenuated the changes in oxidative stress and liver injury. We found positive correlations among indices of oxidative stress (malondialdehyde and inducible nitric oxide synthase) and liver injury (alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase), suggesting that DHV-1 causes significant oxidative damage, which is related to the extent of hepatic injury.Conclusion sIcariin and p-icariin improved the survival and attenuated oxidative stress and liver dysfunction induced by DHV-1. These outcomes were better in ducklings treated with p-icariin than in those treated by icariin. The clinical effects of both components were related to their antioxidant activities.

Icariin-loaded GelMa Hydrogel Encapsulated Potassium Sodium Niobate Biomimetic Piezoelectric Scaffold Regulates Macrophage Polarization to Accelerate Bone Defect Repair

Yongbin Wang,Han Zhang,Zhili Xu,Weihang Zhu,Sheng Chang,Jiahao Wei,Shuqing Chen,Yong Liu,Weiqing Kong,Jianwei Guo

Large bone defects present significant clinical challenges due to limitations of current treatments including immune rejection, infection, and poor osteoinductive capacity. This study developed a novel biomimetic piezoelectric scaffold system combining 3D-printed potassium sodium niobate/nano-hydroxyapatite/polylactic acid (KNN/nHA/PLA) scaffolds with icariin-loaded gelatin methacryloyl hydrogel (ICA@G/NHP) to synergistically promote bone regeneration and immunomodulation. The composite scaffolds demonstrated excellent mechanical properties and stable piezoelectric output under ultrasonic activation. In vitro studies revealed that ultrasonic stimulation was essential for activating piezoelectric effects, significantly enhancing osteogenic differentiation of bone marrow mesenchymal stem cells through upregulation of ALP, RUNX2, and COL1 expression. The incorporated icariin effectively promoted endothelial cell migration and induced M2 macrophage polarization via C-type lectin receptor signaling pathway, creating a pro-regenerative immune microenvironment. In vivo validation using rat cranial and rabbit femoral condyle defect models demonstrated superior bone regeneration with enhanced bone mineral density, bone volume fraction, and mature trabecular architecture compared to controls. Immunofluorescence analysis confirmed sustained M2 macrophage dominance and suppressed inflammatory responses. RNA sequencing identified PI3K/Akt as the central mechanotransduction pathway mediating scaffold effects. This integrated platform addresses dual challenges of osteogenesis and immune regulation, offering a promising therapeutic strategy for critical-sized bone defect repair through ultrasound-activated piezoelectric stimulation combined with targeted immunomodulation.